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A reference for the human genome:The Tetraodon pufferfish sequence
By Birgit Reinert


American and French researchers have recently completed the draft sequence of the freshwater pufferfish Tetraodon nigroviridis. It is the second pufferfish genome sequenced to date. Similar to its Japanese cousin Fugu rubripes, whose draft genome sequence was announced the same day by a different consortium, the genome of Tetraodon is very compact and has remarkably little repetitive DNA, which makes the pufferfish a model vertebrate for the human genome project.

The freshwater pufferfish Tetraodon nigroviridis.

In fact, pufferfish have the smallest known genome among vertebrates, yet roughly the same amount of genes as humans. By comparing the sequencing data to the eight times larger human genome, the scientists are expecting to find human genes and their regulatory sequences more easily.

Jean Weissenbach and colleagues at Genoscope, France's National Sequencing Center in Paris, started the Tetraodon sequencing project in 1997. Four years later, they were joined by a group headed by Eric Lander from the Center for Genome Research at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts.

To identify genes in the human genome, the Genoscope scientists developed a new tool called Exofish (which stands for EXOn FInding by Sequence Homology). Exofish is a genomic comparative method using Tetraodon sequences, which are calibrated to annotate the human genome. The approach is based on the assumption that coding regions are more conserved through evolution than non-coding regions. Shared sequences are presumed to contain genes or regulatory elements that are important, if not essential for vertebrates. The tool has already been used to re-evaluate the number of human genes.

The Tetraodon genome is estimated to be 380 million DNA letters long. It contains 21 chromosome pairs with the largest chromosome still being smaller than the smallest human chromosome. The next steps for the researchers include assembling and annotating the sequence.

The non-toxic freshwater fish lives in the rivers and estuaries of Indonesia, Malaysia and India. On an evolutionary scale, the pufferfish and humans separated about 400 million years ago whereas Tetraodon and Fugu are approximately 20 million years apart.

The most recent Tetraodon sequence data are available online at Genoscope.

See related GNN articles
»A lean model genome: The Japanese pufferfish is sequenced
»The pufferfish: Clues to the human genome puzzle

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Genoscope and Whitehead announce a high sequence coverage of the Tetraodon nigroviridis genome. Press release, Genoscope—Centre National de Séquençage, Evry, France (October 26, 2001).

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